Participants must have progressive CNS lesions, as defined by one of the following:\r\n* Patients may have multiple progressive CNS lesions, some of which have been treated by stereotactic radiosurgery (SRS) or surgery; patients are eligible if they have one or more untreated (by surgery or SRS) progressive lesions that is measurable\r\n* Patients have measurable residual or progressive lesions after surgery\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS are eligible but there needs to be unequivocal evidence of progression of at least one lesion treated by radiation (e.g. tissue diagnosis); biopsy can be considered for definitive diagnosis\r\n* Patients who have previously been treated with systemic therapy for CNS metastases are eligible
COHORT B: Progressive brain metastases after prior local CNS-directed therapy such as radiation or surgery as defined by:\r\n* Untreated measurable lesions in patients that have received surgery and/or SRS to one or more other lesions\r\n* Residual or progressive lesions after surgery if asymptomatic\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS and then whose lesions have progressed are eligible; lesions treated with SRS may be eligible if there is unequivocal evidence of progression
New or progressive CNS lesions, as assessed by the patient’s treating physician\r\n* It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one lesion is measurable (>= 10 mm) per RECIST 1.1; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Patients who have had prior cranial surgery are eligible provided that there is evidence of measurable residual or progressive lesions, and at least 3 months have passed since surgery; if a patient has surgical resection followed by whole brain radiation therapy (WBRT), then there must be evidence of progressive CNS disease after the completion of WBRT\r\n* Patients who had had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions that have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression\r\n* Patient who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such patients must be asymptomatic or minimally symptomatic from their CNS metastases and not requiring corticosteroids
Patients unable to have SRS/SBRT through insurance coverage or ability to pay for SRS/SBRT
Patients unable to have SRS/SBRT through insurance coverage or ability to pay for SRS/SBRT
Participants must have a diagnosis of brain metastases for which SRS is indicated, as determined by a radiation oncologist
Participants must not have more than 5 new or progressive lesions in the brain requiring SRS treatment (greater than 5 total brain lesions are allowed as long as no more than 5 lesions require SRS treatment)
Prior local therapy:\r\n* Prior surgery, whole brain radiation or SRS is allowed as long as the most recent brain progression is amenable to SRS treatment
Unequivocal evidence of new and/or progressive brain metastases, and at least one of the following scenarios:\r\n* Treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable\r\n* Participants who have had prior whole- brain radiation therapy and/or SRS and then whose lesions have subsequently progressed are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS \r\n* Participants who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids for symptom control\r\n* Both participants who present with systemic stable/absent or progressive disease are eligible to this trial, as long as they fulfill one of the above criteria
Concurrent brain directed therapy (beyond SRS and NovoTTF-100M as per protocol)
No prior stereotactic radiosurgery (SRS) to the lesions which will be treated on protocol.
Patients who have had less than or equal to 5 metastases treated with SRS are eligible.
Patients receiving prior stereotactic radiosurgery (SRS) for brain metastases are eligible
Phase I Inclusion Criterion Only: Patients must have brain metastases, treated within 6 weeks of study entry with stereotactic radiosurgery (SRS) resection or whole brain radiation therapy (WBRT); a minimum interval of 3 weeks between completion of brain SRS and/or resection and 6 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
Phase II Inclusion Criterion Only: Patients must have 1-3 brain metastases, each < 3 cm by contrast MRI, treated within 6 weeks of study entry with SRS and/or resection; a minimum interval of 3 weeks between completion of brain SRS and/or resection and the start of treatment in this trial will be observed to allow proper healing; patients with 4 or 5 brain metastases will be evaluated case by case and may be eligible pending on the total field radiated; 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)
Previous cranial SRS/whole brain radiation therapy (WBRT) is allowed if > 3 months prior to single isocenter multi-target (SIMT)
All patients with 1-4 metastatic brain lesions who are considered eligible for single-fraction, frame-based SRS, who are unable or unwilling to undergo frame-based SRS
Prior cranial radiotherapy within 90 days of months of trial enrollment or prior SRS at any time to any lesion to be treated on protocol
Chemotherapy (including oral agents and targeted agents) or immunotherapy given within 14 days of SRS; hormonal therapy is permitted; for Her2+ breast cancer patients, anti-Her2 therapy cannot be given within 14 days of SRS; patients who are scheduled to receive trastuzumab emtansine after SRS cannot be enrolled
At least one brain lesion size >= 0.3 cm in the longest axis amenable to radiation therapy (either via SRS or WBRT)
Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:\r\n* Systemic therapy was administered >= 7 days before SRS\r\n* Radiation was not to the brain\r\n* Surgery to the brain was >= 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
Patients had craniotomy and surgery to the brain within 7 days from the date of SRS
Patients must not be pregnant at the time of SRS treatment
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 4 weeks
Prior brain surgery is allowed, although a lesion situated in the operative bed would not be selected to receive an experimental dose of SRS treatment; SRS should be delivered 4-6 weeks post-surgery if the patient had a craniotomy for resection of a lesion; enrollment of a patient with the goal of performing SRS outside of the 4-6 post-craniotomy window is at the principal investigator (PI)’s discretion
For subjects currently on active systemic cancer therapy, the treating medical oncologist should be consulted to ensure proper washout (if appropriate) periods prior to SRS
Systemic chemotherapy delivered or planned to be delivered within (+/-) 5 days of SRS re-irradiation
Magnetic resonance imaging (MRI) evidence of 1-4 brain metastases, with at least one lesion > 20 mm and =< 50 mm in maximal diameter and determined to be appropriate for SRS and gross total resection; all other brain metastases are appropriate for SRS
Patient can have prior SRS to lesions other than the one planned for neoadjuvant SRS and resection
Subjects will be recruited from patients who are potential candidates for SRS treatment at Dartmouth Hitchcock Medical Center (DHMC) for brain metastases
Any patient undergoing SRS for brain metastases
Patients may have had prior therapy including:\r\n* Whole brain radiation therapy (WBRT) > 3 months ago\r\n* SRS to other brain metastases
Patients receiving SRS to resection bed
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 1-3 metastases with minimum of (6) weeks to the most recent scan are allowed on protocol
Patients must not have received prior whole brain radiation therapy; previous SRS/SRT done at least 3 weeks from the planned start of IPdR therapy is acceptable; SRS/SRT/fractionated boosts or neurosurgery can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Have completed local therapy (surgical resection, WBRT, or SRS) ?14 days prior to initiating abemaciclib and recovered from all acute effects.
Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.
Patients may have brain lesions which measure =< 1cm each; lesions that are > 1 cm that have been treated with stereotactic radiosurgery (SRS) and in the opinion of the PI or his designee no longer represents active disease will also be allowed (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria)
Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target volume would have received more than 12 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
Patients must be candidates for SRS and planning to undergo SRS
Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, with stable systemic disease and ECOG score of 0-2, who would otherwise be eligible for SRS/stereotactic radiation therapy (SRT) alone should not be enrolled into this study unless WBRT is recommended due to any medical reasons or logistic limitations as determined by the treating physician; patients who develop recurrence post-SRS/SRT or surgery alone and are recommended WBRT will be eligible for the protocol
Patients must not have received prior WBRT (previous SRS/SRT done at least 4 weeks from the planned start of WBRT is acceptable); patients planned upfront to undergo SRS/SRT/fractionated boosts or neurosurgery after WBRT are not eligible; however, these treatments/procedures can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).
Diagnosis of CNS metastases for whom SRS or WBRT is indicated, as determined by radiation oncologist assessment
Surgical resection or stereotactic radiosurgery (SRS) to other recurrent lesions in the same patient are acceptable, provided one recurrent lesion remains untreated
Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.
New or progressive CNS lesions, as assessed by the patient’s treating physician, with at least one of the following clinical scenarios:\r\n* It is anticipated that some participants may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Participants who have had prior cranial surgery are eligible, provided that there is evidence of measurable residual or progressive lesions; if a patient has surgical resection followed by whole brain radiation therapy (WBRT) and/or SRS, then there must be evidence of progressive CNS disease after the completion of WBRT and/or SRS\r\n* Participants who have had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS\r\n* Participants who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids
Treating physician must deem that SRS is appropriate treatment for the metastatic spinal lesion(s)
Each SRS target must be the equivalent of =< 3 vertebral levels
For cohorts 1 and 3a/3b, 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)
It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with SRS or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one residual (i.e. non-SRS-treated or non-resected) lesion is measurable (>= 10 mm); the location of the measurable lesion should be documented in the patient chart and case report form
Patients who have had prior WBRT and/or SRS and then whose prior treated lesions have progressed thereafter are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression
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
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)
Planned cytotoxic chemotherapy during the SRS or WBRT
Any stereotactic radiosurgery (SRS) was completed at least 1 week prior to the first dose of study drug.
Patients can have previous brain metastasis that was treated with stereotactic radiosurgery (SRS) if the previously treated lesion is at least 1 cm from the target lesion(s) for this study; the location of the previous SRS treatment location is determined by the SRS MRI
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 (>= 3 lesions) and/or size (>= 1 cm) of brain metastases (BMs); patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible
Patients with prior SRS will also be eligible, provided that there are new, non-irradiated measurable brain lesions
Up to 2 additional intact brain metastases to be treated with stereotactic radiosurgery (SRS) alone
Previous brain radiotherapy (SRS or whole brain radiation therapy [WBRT])
Stereotactic radiosurgery (SRS):\r\n* Patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease\r\n* At least 12 weeks between completion of SRS and initiation of bendamustine
Eligibility for treatment with SRS confirmed by a radiation oncologist
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
Evolving brain lesions post SRS requiring neurosurgical resection (whether for symptomatic control or to establish pathology)