Evaluation of similarity measures for image registration is a challenging problem due to its complex interaction with the underlying optimization, regularization, image type and modality. We propose a single performance metric, named , as part of a new evaluation method which quantifies the effectiveness of similarity measures for brain image registration while eliminating the effects of the other parts of the registration process. We show empirically that similarity measures with higher robustness are more effective in registering degraded images and are also more successful in performing intermodal image registration. Further, we introduce a new similarity measure, called normalized spatial mutual information, for 3D brain image registration whose robustness is shown to be much higher than the existing ones. Consequently, it tolerates greater image degradation and provides more consistent outcomes for intermodal brain image registration.