Jump to:



Intracranial neoplasms are abnormal growths within the cranial cavity that may be composed of benign (non-cancerous) or malignant (cancerous) cells. The tumor may be primary or a metastasis from another location. This article will focus on brain metastases, which are malignant masses that have spread to the brain from a primary cancer located elsewhere in the body.


The most common primary malignancies that metastasize to the brain include lung (~16-20%), melanoma (~7%), renal (7-10%), breast (~5%), and colorectal (1-2%). Brain metastases are about 10 times more common than primary malignant brain tumors and are becoming increasingly common. This is related to more effective therapeutics leading to greater survivorship in cancer patients in addition to advanced imaging and improved screening practices.1

Epidemiology including risk factors and primary prevention

Risk factors include genetics, ionizing radiation, and underlying primary cancer. Brain metastases are the most common type of CNS tumor in the United States, and they may be the first sign of undiagnosed cancer.2 The primary prevention is proper cancer screening and diagnosis.


The most common pathway for spread to the brain is hematogenous. Metastatic tumors are usually at the gray/white junction where blood vessels narrow and trap cells and at terminal arterial watershed areas. Metastatic brain tumors cause various neurologic symptoms due to local invasion and mass effect. Hemorrhage into the tumor may cause a sudden change in clinical presentation. Certain tumor types’ predilection for certain areas of the brain has not been elucidated. Hematologic, lung, breast, melanoma, and gastric cancers can also spread to the leptomeninges. Some tumor types are more responsive to targeted therapies. For example, non-small cell lung cancer frequently expresses EGFR (epidermal growth factor receptor) mutations, melanoma frequently has BRAF mutations, and breast cancer can have HER2 mutations that allow targeted therapies.³ Unfortunately, the treatments for these mutations often do not reach the same therapeutic concentrations in the brain as they do at the primary tumor site.4

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

The progression from primary cancer diagnosis to finding of brain metastasis varies by primary tumor type from 4.5 months (lung cancer) to 41 months (breast cancer). The prognosis is poor but highly variable. If left untreated, the average survival is less than two months. Even with treatment, recurrence is common. Therapies are currently palliative with efforts to increase survival time. At the time of metastasis diagnosis, more than 80% of patients already have multiple brain metastases.5 The most common deficits are impaired cognition (80%), weakness (78%), visual deficits (53%), sensory loss (38%) and bowel and bladder dysfunction (37%).6

Symptoms may include6

  • Impaired cognition
  • Weakness or hemiparesis
  • Visual field defects
  • Sensory loss
  • Bowel and bladder dysfunction
  • Headache
  • Seizures
  • Nausea
  • Vomiting
  • Aphasia
  • Ataxia
  • Dysphagia
  • Personality changes

Specific secondary or associated conditions and complications

May include

  • Brain herniation secondary to increased intracranial pressure
  • Hydrocephalus
  • Seizures
  • Stroke
  • Deep venous thrombosis
  • Endocrine abnormalities
  • Paraneoplastic phenomena

Essentials of Assessment


Details of treatments of diagnosed cancer, specifically radiation dose, surgery, and chemotherapy.

Review of systems:

  • Headache
  • Seizures
  • Nausea/vomiting
  • Motor changes such as weakness or coordination problems
  • Sensory and/or visual changes.
  • Cognitive issues such as memory or attention deficits
  • Swallowing difficulty
  • Fatigue

Past personal or family history of cancer. Substance use including tobacco use.

Preventative screening tests such as mammograms, pap smears, colonoscopies, digital prostate exams, and prostate specific antigen (PSA) tests should be obtained.

It is important to get details of the recent and current functional status for both basic and instrumental activities of daily living, vocation, and avocation.

Physical examination

A focused neurological and musculoskeletal examination should include:

  • Cognitive assessment/screen
  • Cranial nerve examination
  • Language assessment
  • Manual muscle testing
  • Sensory exam
  • Coordination testing
  • Reflex examination
  • Gait evaluation

Functional assessment

Interdisciplinary evaluation with physical, occupational and speech therapists and neuropsychology to assess ADLs and cognitive function.

  • Some tests that may be utilized by these specialists include but are not limited to the following:
    • Functional Independence Measures (FIM)
    • Balance
      •  Berg Balance Scale
    • Gait/strength/endurance
      • Get Up and Go
      • Timed 10-meter walk test
      • 6-minute walk test

Laboratory studies

Lab work-up should include electrolytes, liver function tests, blood urea nitrogen, creatinine, albumin, and complete blood count. Specialized tests may be indicated for tumor progression/recurrence and pituitary function.


Initial imaging will include brain magnetic resonance imaging, with gadolinium to assess the tumor itself, and depending on tumor type, chest imaging or spine imaging may also be ordered to assess other sites. Positron emission scan (PET) scan may also be ordered depending on clinical need to look for metastases, often in conjunction with computerized tomography scan. Imaging may be needed when there is a change in clinical condition to assess for edema, change in tumor size or burden, and hydrocephalus.

Supplemental assessment tools

  • Electrodiagnostic testing
  • Brain biopsy to ascertain primary tumor type and to determine if recurrence or post treatment changes.
  • Electroencephalogram if question of seizures. 
  • Modified barium swallow or FEES to evaluate for dysphagia.

Early predictors of outcomes

Primary tumor prognosis depends most on histology. Age of the patient, size, location of the lesion, tumor burden and presence of mass effect affect prognosis. For metastatic tumors, the primary tumor and tumor factors such as radiosensitivity/chemosensitivity affect prognosis. Isolated metastasis can often be resected and have a better prognosis than multiple metastases.

Measurement of patient outcomes

  • Eastern cooperative Oncology Group (ECOG)
  • Karnofsky Performance Scale (KPS)
  • Disability Rating Scale


Identify what assistive devices and modifications are needed to move safely in the home and the community.

Social role and social support system

  • Shared decision making with patient and family regarding goals of care, functional independence, return to work, avocation.
  • Palliative care and hospice referral as appropriate.
  • Social work referral as appropriate to assess needs and available resources.
  • Assist family/friends in planning how to cope with day to day needs of the patient as well as long term related to diagnosis. Discuss psychology referral.
  • Identify support groups for the family as well as the patient.
  • Identify financial resources at the hospital system and/in the community for care.
  • Patient education of community and national resources and organizations such as the American Cancer Society

Rehabilitation Management and Treatments

At different disease stages

New onset/acute

  • Potential curative interventions: Surgery and chemotherapy. Radiation therapy: whole brain vs stereotactic radiosurgery.
  • Medical complications:
    • Pain: physical therapy, medications, or injections
    • Wound care: monitor any surgical incisions and monitor for infection.
    • Seizure: Antiepileptic medications
    • Early radiation reactions: Nausea, vomiting, alopecia, tinnitus and skin changes.
    • Drug adverse reactions: monitor for constipation, neuropathy, etc.
  • Rehabilitation: Rehabilitation requires a multidisciplinary approach due to presence of multiple symptoms. For example, brain tumor patients admitted to inpatient rehabilitation facilities (IRF), approximately 75% of them had three or more concurrent neurological deficits and 39% of patients had five or more deficits. Some improvements noted over prior decades show shorter length of stay and lower admission FIM scores. Discharge to the community remains high.6
    • Functional outcomes: Functional outcomes for patients with brain tumor admitted to IRF remain similar to those with TBI and stroke when matched by age, sex, and admission functional status.7-11
    • Survival: Though the data is sparse there has some conflicting data regarding survival in relation to admission to IRF.12 A proposed hypothesis to this data is that “a structured inpatient rehabilitation program may level the survival field in lower-functioning patients who otherwise may be faced with a dismal prognosis”.9
    • Barriers to Rehabilitation
      • In a 3-year retrospective study of all patients admitted to all US acute IRFs only 2.4% of these were patients with oncological diseases.13
      • “Cancer” does not fall under the CMS 13 diagnoses set forth by Medicare. Though brain tumors can be categorized under the diagnosis of “brain injury” and similarly with spinal tumors under “spinal cord injury”.
      • IRFs may be unable to provide specialized cancer care and often specific oncological treatment must be delayed. From a recent study specifically in brain tumor patients showed a IRF median length of stay of 10 days. No change was noted in overall survival, but it was hypothesized that for certain situation this could have unfortunate consequences.
  • In the cases where further surgical tumor resection was necessary several studies have shown similar functional improvement and discharge to home rate (64-78%) from IRF in initial vs repeat resection.10,15


  • Secondary prevention and disease management strategies:
    • Radiation and chemotherapy.
    • Monitor for radiation encephalopathy.
    • Late delayed radiation can cause focal cerebral necrosis or diffuse injury.
    • Minimize risk of other complications, such as osteoporosis leading to fracture.
    • Promote adequate nutrition for skin integrity and muscle mass maintenance.
  • Symptom relief is similar to acute management above with addition of the following:
    • Mood disorders: Psychology and or medications
    • Fatigue: Fatigue is often multifactorial.
      • Differential includes deconditioning, medication side effects, anemia, endocrine disorders, sleep disorders, mood disorders. 
    • Cognitive functioning
      • The Congress of Neurological Surgeons’ guidelines for the treatment of adults with metastatic brain tumors recommends memantine for patients receiving whole brain radiation therapy (WBRT). Evidence supports placing “patients having WBRT (given for either existing brain metastases or as prophylactic cranial irradiation) on 6 months of memantine to potentially delay, lessen, or prevent the associated neurocognitive toxicity. The evidence for donepezil is moderate, and there is insufficient evidence that methylphenidate is beneficial. There is additional evidence suggesting that HA WBRT may significantly reduce the risk of neurocognitive decline compared with conventional WBRT”.16
  • Rehabilitation
    • Comprehensive non-traumatic brain injury program including physical therapy, occupational therapy, and speech therapy.
    • Neuropsychological testing as needed for cognitive deficits.
    • Orthoses if needed.


  • Secondary prevention and disease management strategies:
    • Imaging to address growth/recurrence of primary tumor and metastatic disease.
  • Symptom relief: Similar to acute and subacute management above.
  • Rehabilitation strategies that intend to optimize function: Similar to acute and subacute management above.

End of life care

  • Symptom relief
    • Pain management
    • Treatment of mood disorders through counseling and medications
    • Include social work to support family/caregiver needs as patient independence and mobility declines
    • Supportive care as needed

Coordination of care

Treatment of brain tumors requires a multidisciplinary team including neurosurgeons, oncologists, radiation oncologists, primary care physicians, palliative care, physiatrists, rehabilitation therapists, psychologists, social workers, and pastoral care. The focus should be on the patients’ goals of improving or maintaining quality of life and dignity.

Patient & family education

Accurate and consistent information should be provided to the family by all care providers. This is especially key as far as life expectancy is concerned. If cognition is impaired, behavioral strategies may be needed to ensure safety.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Screening for cognitive deficits should be implemented as these are common in patients with brain tumors. Education regarding these deficits should be given to both patients and caregivers. Collaboration with oncologists will help address functional outcome measures and address practical needs of patients and caregivers. Palliative care programs need to include a functional component and integration of PMR into care plans.

Cutting Edge/Emerging and Unique Concepts and Practice

Stereotactic Radiosurgery (SRS) has become the standard of care in cases of lower brain tumor burden. SRS uses Proton therapy which delivers a high level of focused proton beams to the tumor with the goal of limiting exposure to the neighboring brain tissues. New surgical technologies may include fluorescent imaging during surgery to help differentiate tumor tissue from healthy brain tissue. Functional MRI scans can help with surgical planning by highlighting where certain functional areas are located within the brain so that these areas can be avoided during radiation or surgery. Immunotherapy is an emerging treatment and studies are continuing to elucidate optimal treatments for specific tumor targets. New efforts to spare the hippocampus during whole brain radiation therapy has been shown to decrease post-radiation neurocognitive decline especially when combined with memantine.17 In addition, many academic medical centers have multiple clinical trials available for patient enrollment. It is recommended that patients receive a palliative care consultation at the time of diagnosis of brain metastasis. Palliative care has been shown to improve quality of life, decrease symptoms of depression, and prolong life.18 There is evidence that cognitive rehabilitation improves cognitive functioning in the acute and post-acute settings.19

Gaps in the Evidence-Based Knowledge

The optimal timing of rehabilitation for brain metastasis remains undefined. Future studies should also attempt to optimize treatment combinations (immunotherapy, whole brain and stereotactic radiation, corticosteroids, rehab therapy) that increase survival and quality of life in different tumor types.


  1. Lowery FJ, Yu D. Brain metastasis: Unique challenges and open opportunities. Biochimica et Biophysica Acta (BBA) – Reviews on Cancer. 2017;1867(1):49-57. doi:10.1016/j.bbcan.2016.12.001
  2. Ostrom QT, Wright CH, Barnholtz-Sloan JS. Chapter 2 – Brain metastases: epidemiology. In: Schiff D, van den Bent MJ, eds. Handbook of Clinical Neurology. Vol 149. Metastatic Disease of the Nervous System. Elsevier; 2018:27-42. doi:10.1016/B978-0-12-811161-1.00002-5
  3. Lin NU. Targeted therapies in brain metastases. Curr Treat Options Neurol. 2014;16(1):276
  4. Fokas E, Steinbach JP, Rodel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61–75.
  5. Markesbery WR, Brooks WH, Gupta GD, Young AB. Treatment for patients with cerebral metastases. Arch Neurol. 1978;35(11):754–6.
  6. Mukand JA, Blackinton DD, Crincoli MG, Lee JJ, Santos BB. Incidence of neurologic deficits and rehabilitation of patients with brain tumors. Am J Phys Med Rehabil. 2001;80:346-350.
  7. O’Dell MW, Barr K, Spanier D, Warnick RE. Functional outcome of inpatient rehabilitation in persons with brain tumors. Arch Phys Med Rehabil 1998:79:1530-1534.
  8. Huang ME, Wartella JE, Kreutzer JS. Functional outcomes and quality of life in patients with brain tumors: a preliminary report. Arch Phys Med Rehabil. 2001;82(11):1540-46.
  9. Roberts PS, Nuño M, Sherman D, et al. The impact of inpatient rehabilitation on function and survival of newly diagnosed patients with glioblastoma. PM R. 2014;6(6):514-521. doi:10.1016/j.pmrj.2013.12.007
  10. Reilly JM, Gundersen AI, Silver JK, Tan CO, Knowlton SE. A Comparison of Functional Outcomes between Patients Admitted to Inpatient Rehabilitation after Initial Diagnosis Versus Recurrence of Glioblastoma Multiforme. PM R. 2020;12(10):975-983. doi:10.1002/pmrj.12379
  11. Yu J, Jung Y, Park J, et al. Intensive Rehabilitation Therapy Following Brain Tumor Surgery: A Pilot Study of Effectiveness and Long-Term Satisfaction. Ann Rehabil Med. 2019;43(2):129-141. doi:10.5535/arm.2019.43.2.129
  12. Tang V, Rathbone M, Park Dorsay J, Jiang S, Harvey D. Rehabilitation in primary and metastatic brain tumors: impact of functional outcomes on survival. J Neurol. 2008;255(6):820-827. doi:10.1007/s00415-008-0695-z
  13. Mix JM, Granger CV, LaMonte MJ, et al. Characterization of Cancer Patients in Inpatient Rehabilitation Facilities: A Retrospective Cohort Study. Arch Phys Med Rehabil. 2017;98(5):971-980. doi:10.1016/j.apmr.2016.12.023
  14. Warren KT, Liu L, Liu Y, et al. Time to treatment initiation and outcomes in high-grade glioma patients in rehabilitation: a retrospective cohort study. CNS Oncol. 2020;9(4):CNS64. doi:10.2217/cns-2020-0018
  15. Chowdhury N, Scott C, O’Dell MW. Recovery in glioblastoma multiforme during inpatient rehabilitation is equivalent in first versus repeat resection: A 10-year retrospective analysis. PM R. 2022;14(1):40-45. doi:10.1002/pmrj.12573
  16. The Role of Whole Brain Radiation Therapy in Adults with Newly Diagnosed Metastatic Brain Tumors – cns.org  https://www.cns.org/guidelines/browse-guidelines-detail/guideline-on-role-of-whole-brain-radiation-therapy
  17. Whole-Brain radiation therapy with or without hippocampal avoidance in treating patients with limited stage or extensive stage small cell lung cancer – Full text view – ClinicalTrials.gov. (n.d.). https://classic.clinicaltrials.gov/ct2/show/NCT02635009?term=NRG-CC003&rank=1
  18. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non–small-cell lung cancer. N Engl J Med. 2010;363(8):733-742. doi:10.1056/NEJMoa1000678
  19. Weyer-Jamora C, Brie MS, Luks TL, Smith EM, Hervey-Jumper SL, Taylor JW. Postacute cognitive rehabilitation for adult brain tumor patients. Neurosurgery. 2021;89(6):945-953. doi:10.1093/neuros/nyaa552

Original Version of the Topic

Rina Bloch, MD. Intracranial Neoplasms. 11/11/2011.

Previous Revision(s) of the Topic

Rina Bloch, MD. Intracranial Neoplasms. 11/11/2011.

Whitney Luke, MD. Brain Metastasis. 5/12/2021

Author Disclosures

Nandita Keole, MD
Nothing to Disclose

Sally Alcott, MD
Nothing to Disclose

Daniel Wei, MD
Nothing to Disclose

Zeke Clemmens, DO
Nothing to Disclose

Erik Anderson, DO
Nothing to Disclose