Participants with known brain metastases will be eligible if they have completed the primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection) and if they have remained clinically stable, asymptomatic and off of steroids for at least  days before starting study treatment.
COHORT D: - brain metastases (where stereotactic radiosurgery would be indicated)
Participants who have received prior treatment with interstitial brachytherapy, stereotactic radiosurgery, or implanted chemotherapy sources, such as wafers of polifeprosan  with carmustine
Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery and the disease has been confirmed stable (i.e., no increase in lesion size) for at least  weeks with two consecutive magnetic resonance imaging (MRI) scans using contrast prior to study day ; enzyme inducing anticonvulsants are not allowed while patients are on study treatment
CNS metastases, unless treated w/ surgery, whole brain radiation or stereotactic radiosurgery, and stable disease ? wks w/o steroid use for ? wks prior to study drug
Planning of any brain local treatment (including but not limited to surgery, stereotactic radiosurgery, whole brain radiation, intrathecal chemotherapy) following the administration of the first dose of study drug.
Received prior local therapy (stereotactic radiosurgery, brachytherapy, or carmustine wafers) to the proposed area of MLA treatment
Disease confined to locoregional site and can be encompassed in a stereotactic body radiosurgery portal
No prior stereotactic radiosurgery (SRS) to the lesions which will be treated on protocol.
Stereotactic radiosurgery candidate per radiation oncologist
Surgery unable to be performed between    days after radiosurgery
Radiotherapy (except for brain and extremities or stereotactic treatment) within the past  weeks prior to treatment with the trial drug
Have up to five measurable (by Response Assessment in Neuro-Oncology Criteria [RANO]) brain metastasis planned for stereotactic radiosurgery
Patients treated metastatic lesions to the brain may be enrolled after completing stereotactic radiosurgery (may enroll  days after treatment) or whole brain radiation (may enroll  days after treatment) and being weaned off corticosteroids (may enroll  days after weaning)
Patients with untreated brain metastasis; patients with metastatic lesions to the brain may be enrolled after completing stereotactic radiosurgery or whole brain radiation (may enroll  days after treatment and must be off corticosteroids for at least  days prior to the start of study treatment
Previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery, and
Patients receiving prior stereotactic radiosurgery (SRS) for brain metastases are eligible
Phase I Inclusion Criterion Only: Patients must have brain metastases, treated within  weeks of study entry with stereotactic radiosurgery (SRS) resection or whole brain radiation therapy (WBRT); a minimum interval of  weeks between completion of brain SRS and/or resection and  weeks for WBRT and the start of treatment  in this trial will be observed to allow proper healing; the presence of concomitant extracranial metastatic disease is allowed for enrollment
Symptomatic brain metastases requiring immediate local interventions such as craniotomy or stereotactic radiosurgery (SRS)
Patients who have received radiation to brain and/or spine, including whole brain radiation, stereotactic radiosurgery, or stereotactic body radiation therapy (SBRT), are eligible, but must have completed radiation treatment at least  days prior to the start of treatment
Patients must not have had prior treatment of glioblastoma with stereotactic radiosurgery, brachytherapy, or carmustine-impregnated wafers (Gliadel).
Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery
Patient may have had prior therapy for brain metastasis, including radiosurgery and surgical resection however must have completed prior resection and radiosurgery at least  days before enrollment and not received further active treatment
Prior radiation therapy to the brain besides radiosurgery
Patients with untreated central nervous system (CNS) metastases; patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiotherapy, focal radiotherapy, and stereotactic radiosurgery) ending at least  weeks prior to randomization, or after surgical resection performed at least  days prior to randomization; the patient may have no evidence of grade >=  CNS hemorrhage based on pretreatment MRI or IV contrast CT scan (performed within  days before randomization)
The additional lesions will each be treated with stereotactic radiosurgery
Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected without recurrence or treated with stereotactic radiosurgery (SRS) without progression x  weeks
Patients with ? newly diagnosed brain metastases deemed to be eligible for radiosurgery\r\n* Prior whole brain radiotherapy (RT) and radiosurgery (to areas outside of the newly diagnosed brain metastases requiring radiosurgery) is allowed
Participants with known central nervous system (CNS) primary tumors or metastases who have completed brain therapy (such as radiotherapy, stereotactic radiosurgery, or surgical resection) and have remained clinically stable, asymptomatic, and off of steroids for  weeks prior to Cycle  Day  will be eligible.
Prior whole/partial brain irradiation or stereotactic radiosurgery
Brain metastases or bone metastases; patients with brain metastases must have received treatment for them (resection or stereotactic radiosurgery [SRS]) and these metastatic foci must be stable for  weeks prior to starting study drug
Eligibility for stereotactic radiosurgery using magnetic resonance imaging (MRI) targeting: The decision to treat with stereotactic radiosurgery will be made by a consensus of the radiation oncology, neurosurgery and neuro-oncology providers or their alternates at the weekly Brain Tumor or Stereotactic Radiosurgery Tumor Conferences; all patients must have no restrictions to obtaining MRI with and without paramagnetic contrast
Prior radiosurgery
The additional lesions will each be treated with single fraction stereotactic radiosurgery
Patients will be excluded if they have had prior whole brain radiotherapy (WBRT) or prophylactic cranial irradiation (PCI); prior SRS or gamma knife radiosurgery to - metastases with minimum of () weeks to the most recent scan are allowed on protocol
Patients with a radiosurgery boost or fractionated stereotactic boost as a part of their treatment plan are not eligible
Presence of brain metastases, unless the patient received brain irradiation, including adequate stereotactic radiosurgery, at least  weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least  weeks prior to randomization
At least  days passed since last brain surgery, or intracranial radiation therapy/radiosurgery
Patients with treated brain metastases are eligible for study participation; patients may not receive ongoing treatment with steroids at screening; anticonvulsants (at stable dose) are allowed; treatment for brain metastases may be whole?brain radiotherapy, radiosurgery, neurosurgery, or a combination as deemed appropriate by the treating physician; radiotherapy and stereotactic radiosurgery must be completed at least  days prior to randomization
Patients who receive stereotactic radiosurgery or whole brain radiation for brain metastases are eligible only if they are asymptomatic and have stable MRI scans for  consecutive months, including =<  days of study registration
Patients with brain metastases are allowed provided that:\r\n* No leptomeningeal disease is present\r\n* Intracranial disease is controlled by prior local therapies (craniotomy, stereotactic radiosurgery, whole brain irradiation), as evidenced by brain MRI  weeks post treatment indicating no new intracranial disease\r\n* Stable or decreasing dose of steroids provided patient on =<  mg of prednisone or its equivalent daily
Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target volume would have received more than  Gy
Brain metastases from breast cancer with or without prior treatment; whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) or surgical resection permitted through progression; progression must be documented in an at least one lesion untreated by SRS or in any site after surgery or WBRT
Prior radiation therapy to the whole brain (prior stereotactic radiosurgery or fractionated stereotactic radiation therapy to focal areas is allowed)
Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of  days prior to study treatment
Progression of or new brain metastases after completion of whole-brain radiotherapy or stereotactic radiosurgery
Completion of whole-brain radiotherapy or stereotactic radiosurgery more than  days prior to enrollment
Participants with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection will be eligible if they have remained clinically stable, asymptomatic, and off steroids for  month prior to enrollment.
At least  days for stereotactic radiosurgery
Received chemotherapy or radiation within  days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).
No prior interstitial brachytherapy or stereotactic radiosurgery unless area of assessment and planned resection is outside the region previously treated.
Patients with a history of pituitary irradiation can be included, provided that at least  years (stereotactic radiosurgery) or  years (conventional radiation) have elapsed from the time of last radiation treatment to the time of enrollment into this study.
Surgical resection or stereotactic radiosurgery (SRS) to other recurrent lesions in the same patient are acceptable, provided one recurrent lesion remains untreated
Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery
Patients must have previously received at least one CNS directed treatment (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgery
Received cytotoxic chemotherapy, investigational agents, or radiation within  days, except SRS or stereotactic body radiosurgery.
Radiosurgery including Gamma Knife, linear accelerator based radiosurgery, CyberKnife and placement of Gliadel wafer
at least  weeks since craniotomy and resection or stereotactic radiosurgery
Patients with brain metastasis are eligible for participation ONLY if they have been treated with definitive surgery or radiation (surgery +/- radiotherapy, radiosurgery, or gamma knife) and meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior  week interval
Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for  weeks are eligible.
Patients must have received prior radiotherapy for meningioma; patients may have received standard external beam radiation, interstitial brachytherapy, or radiosurgery in any combination; an interval of >=  weeks ( days) must have elapsed from the completion of radiotherapy to study entry and there must be subsequent evidence of tumor progression; patients with prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progression disease rather than radiation necrosis based on positron emission tomography (PET), MR-perfusion, MR-spectroscopy, or surgical documentation of disease; if there is any question, investigators should discuss with the MSKCC principal investigator (PI)
 weeks ( days) from any radiation treatment, stereotactic radiosurgery, conventional surgery, or chemotherapy
Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection will be eligible if they have remained clinically stable, asymptomatic and off of steroids for  days.
Prior radiation or radiosurgery to the involved level of the spine
Patients previously treated with stereotactic radiosurgery, stereotactic radiotherapy, brachytherapy, Gliadel wafers or other intratumoral chemotherapy are eligible
Patients with central nervous system (CNS) progression are ineligible until this CNS progression is treated either with whole brain radiation or stereotactic radiosurgery (SRS) and have an magnetic resonance imaging (MRI) of the affected CNS lesion(s)  months after radiation therapy (per National Comprehensive Cancer Network [NCCN] guidelines) demonstrating stable (or improved) disease prior to proceeding with enrollment on the AVX study; patients also must be off all steroids prior to initiating the AVX protocol
For cohorts  and a/b, patients must have new or progressive measurable central CNS lesions, as assessed by the patient's treating physician; this includes patients who have progressed after at least one line of standard treatment for CNS disease (whole brain radiotherapy [WBRT], stereotactic radiosurgery [SRS], or surgical resection as below)
For patients who undergo surgery, postoperative whole brain radiation therapy will not be allowed while patients are on study; patients will require discontinuation of neratinib if WBRT will be administered; however, if the treating provider feels that targeted radiosurgery (SRS, gamma knife, etc) would be of benefit postoperatively, patients may proceed with this and then begin neratinib AFTER radiation completes
Prior treatment with intracystic P-, intracystic bleomycin or radiosurgery
Patients with measurable brain metastasis who have not been or will not be treated with stereotactic radiosurgery (SRS) or surgical resection (Note: these treatment options are only permitted at relapse)
Patients who had radiosurgery >  months prior to registration are eligible
Prior treatment with radiosurgery
Able to be treated with either a gamma knife or a linear accelerator-based radiosurgery system
Prior intracranial radiation therapy (whole brain radiation therapy, stereotactic radiosurgery, gamma knife, or equivalent) is allowed, but not required
Subjects with known brain metastases will be eligible if they have completed the primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection) and if they have remained clinically stable, asymptomatic, and off of steroids for at least  days
Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) ? days prior to the first dose of study treatment,
Patients who have had prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as gliosis/scarring from these modalities may limit delivery; however, if a patient has a resection or biopsy at the site of prior stereotactic radiotherapy, convection enhanced delivery, or brachytherapy and the biopsy specimen shows recurrent GBM and EGFR amplification by FISH, the patient will be eligible; patients with recurrence outside the radiosurgery field will be considered for eligibility if the recurrence is clearly documented to be outside the field and more than  months have lapsed since the last dose of radiosurgery
Patients will be allowed to participate following single prior CNS treatment with stereotactic radiotherapy whole brain irradiation and stable without steroid requirement for ? months or following ? prior CNS treatments with stereotactic radiotherapy whole brain irradiation and stable without steroid requirement for ? months.
Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases is eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring systemic steroids and any whole brain radiation therapy was completed at least  weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least  week prior to study drug administration.
 days for cytotoxic chemotherapy, immunotherapy, whole brain radiotherapy, anticonvulsive therapy, stereotactic radiosurgery and major surgery
Any stereotactic radiosurgery (SRS) was completed at least  week prior to the first dose of study drug.
Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >=  weeks prior to enrollment, and are asymptomatic with no corticosteroid requirements for >=  weeks prior to randomization, and no enzyme inducing anticonvulsants for >=  weeks prior to randomization); brain MRI or CT is required at screening
Brain metastases are excluded unless treated and shown to be controlled more than  month from after craniotomy or more than  weeks after gamma knife radiosurgery and not associated with central nervous system (CNS) symptoms
Concurrent or previous anti-cancer chemotherapy, immunotherapy or investigational agents <  weeks, or palliative radiation <  weeks prior to the first day of study treatment. Patients who receive gamma knife radiosurgery for brain metastases or whole brain radiation are eligible if gamma knife radiosurgery was performed >  weeks before treatment is started or whole brain radiation was performed >  weeks before treatment is started, and are clinically stable.
Patients can have previous brain metastasis that was treated with stereotactic radiosurgery (SRS) if the previously treated lesion is at least  cm from the target lesion(s) for this study; the location of the previous SRS treatment location is determined by the SRS MRI
Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery and the disease has been confirmed stable (i.e., no increase in lesion size, and stable or decreased doses of corticosteroids) for at least  weeks with two consecutive scans prior to Study Day  (Parts  and ) or randomization (Part ). (Enzyme inducing anticonvulsants are not allowed while subjects are on study treatment. Prior whole-brain radiation as adjuvant treatment is allowed.)
Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe.
Subjects with active central nervous system (CNS) disease are excluded; patient with brain metastases previously treated with surgery or stereotactic radiosurgery and with confirmed stable disease (SD) for >=  weeks are allowed
Prior Central Nervous System (CNS)-directed local therapies, including surgical resection, whole brain radiation (WBRT), Stereotactic radiosurgery (SRS), or gamma knife (GK)
Planned WBRT based on number (>=  lesions) and/or size (>=  cm) of brain metastases (BMs); patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible
Up to  additional intact brain metastases to be treated with stereotactic radiosurgery (SRS) alone
Participants with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least  days prior to randomization, or after surgical resection performed at least  days prior to randomization. The participant may have no evidence of Grade  (or greater) Central Nervous System (CNS) hemorrhage based on pretreatment scans(performed within  days before randomization).
Subjects with brain metastases are excluded, unless a. All known lesions must be previously treated with surgery or stereotactic radiosurgery, and- b. Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for ? days prior to first dose on study (must be documented with two consecutive MRI or CT scans using contrast), and c. Asymptomatic with no corticosteroids requirement for ?  days prior to first dose on study, and d. No enzyme-inducing anticonvulsants for ?  days prior to first dose on study.
Patients who have undergone stereotactic radiosurgery prior to or following surgical resection, or the placement of Gliadel Wafers.
Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least  weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least  week prior the first dose of study drug.
Medical treatment plan includes whole-brain radiation therapy and/or stereotactic radiosurgery
Not eligible for Stereotactic Radiosurgery (SRS) treatment of brain tumor.
Patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible
Patient with metastatic brain tumors greater than or equal to . cm that will be treated with stereotactic radiosurgery and scheduled for an MRI scan as part of their routine care
Completed fractionated radiation therapy (to  Gy for high grade gliomas) or stereotactic radiosurgery or hypofractionated radiation therapy (e.g. for brain metastases, anaplastic meningiomas), without or with concurrent chemotherapy
Patients who have been or are anticipated to be treated with radiosurgery
Prior re-irradiation or stereotactic radiosurgery for recurrent disease at the same tumor location intended for HFRT in this study
Participants with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic, and off steroids for one month.